This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 3/24/2008 It is well accepted that reduced cognitive functioning,33 depression34 and fatigue35-37 are much more prevalent in individuals with TBI than in the general population, and the treatment of these disorders represents a key challenge to the rehabilitation and improved quality of life of persons with TBI. Although aerobic exercise has been shown to improve cognition and mood in the general population,38-45 research in individuals with TBI is limited.46-50 However, exercise has been shown to be effective in improving cognition, depression and fatigue in individuals with other medical conditions, such as cancer,51 multiple sclerosis (MS),52 fibromyalgia,53 dementia,54-56 chronic fatigue syndrome,57 chronic obstructive pulmonary disease,58 and in the elderly.44,59,60 While an aerobic exercise treatment program may be similarly effective for individuals with TBI, research does not yet support this premise. The proposed study will a) examine the efficacy of an aerobic exercise intervention for improving cognition, depression and fatigue after TBI, b) evaluate the effect of post-TBI exercise on life satisfaction, and c) explore personal and injury characteristics that mediate effectiveness of aerobic exercise in individuals with TBI. The effects of the intervention will be examined using a randomized clinical trial with a crossover design evaluating objective and subjective effects of a 16-week aerobic exercise program. More specifically, each person will undergo individual interviews, self reports and neuropsychological testing aimed at measuring cognition, mood, fatigue, and life satisfaction. Approximately 112 individuals who meet all eligibility criteria are expected to complete the entire study. Assessment of cognition, mood, fatigue, and life satisfaction will occur prior to beginning the intervention, immediately after the intervention and three months post-intervention. The study will also examine the role of neurotropic growth factors (BDNF and VEGF) in improving emotional function, cognitive performance, and fatigue. Hypothesis: Cognitive functioning, mood, and fatigue symptoms will improve following eight weeks of exercise intervention. This improvement will correlate with increased BDNF and VEGF levels.